A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability.

Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1'-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the I isotope). The PET imaging ability and ex vivo biodistribution of [ I]4 were compared with the well-studied methyl [3-( 1'-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [ I]2) and [ F]fluorodeoxyglucose ([ F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [ I]4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [ F]FDG and [ I]2 in 2 % ethanol formulation, [ I]4, at the same radioactive dose (25 μCi per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2, which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [ I]4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types-brain, renal carcinomas, pancreas-in which [ F]FDG shows limitations.